Maternal deprivation and adolescent cannabinoid exposure impact hippocampal astrocytes, CB1 receptors and brain-derived neurotrophic factor in a sexually dimorphic fashion

Neuroscience. 2012 Mar 1;204:90-103. doi: 10.1016/j.neuroscience.2011.09.063. Epub 2011 Oct 6.


We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9-10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/kg, PND 28-42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug "per se" induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cannabinoids / pharmacology*
  • Cyclohexanols / pharmacology
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Maternal Deprivation*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Sex Characteristics*


  • Brain-Derived Neurotrophic Factor
  • Cannabinoids
  • Cyclohexanols
  • Receptor, Cannabinoid, CB1
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol